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Neutralizing BAFF/APRIL with atacicept prevents early DSA formation and AMR development in T cell depletion induced nonhuman primate AMR model.

dc.contributor.author Kwun, J
dc.contributor.author Page, E
dc.contributor.author Hong, JJ
dc.contributor.author Gibby, A
dc.contributor.author Yoon, J
dc.contributor.author Farris, AB
dc.contributor.author Villinger, F
dc.contributor.author Knechtle, S
dc.coverage.spatial United States
dc.date.accessioned 2015-05-14T18:34:33Z
dc.date.issued 2015-03
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/25675879
dc.identifier.uri https://hdl.handle.net/10161/10054
dc.description.abstract Depletional strategies directed toward achieving tolerance induction in organ transplantation have been associated with an increased incidence and risk of antibody-mediated rejection (AMR) and graft injury. Our clinical data suggest correlation of increased serum B cell activating factor/survival factor (BAFF) with increased risk of antibody-mediated rejection in alemtuzumab treated patients. In the present study, we tested the ability of BAFF blockade (TACI-Ig) in a nonhuman primate AMR model to prevent alloantibody production and prolong allograft survival. Three animals received the AMR inducing regimen (CD3-IT/alefacept/tacrolimus) with TACI-Ig (atacicept), compared to five control animals treated with the AMR inducing regimen only. TACI-Ig treatment lead to decreased levels of DSA in treated animals at 2 and 4 weeks posttransplantation (p < 0.05). In addition, peripheral B cell numbers were significantly lower at 6 weeks posttransplantation. However, it provided only a marginal increase in graft survival (59 ± 22 vs. 102 ± 47 days; p = 0.11). Histological analysis revealed a substantial reduction in findings typically associated with humoral rejection with atacicept treatment. More T cell rejection findings were observed with increased graft T cell infiltration in atacicept treatment, likely secondary to the graft prolongation. We show that BAFF/APRIL blockade using concomitant TACI-Ig treatment reduced the humoral portion of rejection in our depletion-induced preclinical AMR model.
dc.language eng
dc.publisher Wiley
dc.relation.ispartof Am J Transplant
dc.relation.isversionof 10.1111/ajt.13045
dc.subject B cell biology
dc.subject alloantibody
dc.subject animal models: nonhuman primate
dc.subject basic (laboratory) research/science
dc.subject immunosuppression/immune modulation
dc.subject kidney transplantation/nephrology
dc.subject rejection: antibody-mediated (ABMR)
dc.subject translational research/science
dc.subject Animals
dc.subject Antibodies, Neutralizing
dc.subject Antibody Formation
dc.subject B-Cell Activating Factor
dc.subject Graft Survival
dc.subject Humans
dc.subject Kidney Transplantation
dc.subject Lymphocyte Depletion
dc.subject Macaca mulatta
dc.subject Male
dc.subject Models, Animal
dc.subject Recombinant Fusion Proteins
dc.subject T-Lymphocytes
dc.subject Tumor Necrosis Factor Ligand Superfamily Member 13
dc.title Neutralizing BAFF/APRIL with atacicept prevents early DSA formation and AMR development in T cell depletion induced nonhuman primate AMR model.
dc.type Journal article
duke.contributor.id Kwun, J|0669479
duke.contributor.id Knechtle, S|0167915
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/25675879
pubs.begin-page 815
pubs.end-page 822
pubs.issue 3
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Abdominal Transplant Surgery
pubs.publication-status Published
pubs.volume 15
dc.identifier.eissn 1600-6143
duke.contributor.orcid Kwun, J|0000-0002-8563-5472
duke.contributor.orcid Knechtle, S|0000-0002-1625-385X


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